Antidepressants for generalized anxiety disorder (GAD)

In the past, people with generalized anxiety disorder (GAD) were usually treated with drugs designed to reduce anxiety (called anxiolytics). There is growing evidence that drugs used to treat depression (antidepressants) may also be helpful for people with GAD. We therefore reviewed clinical trials of the use of antidepressants in GAD . Fifteen published trials were included. Of these trials, eight used recognized methods for diagnosing GAD and gave useful data (Rickels 1993; Rocca 1997; Davidson 1999 a; Gelenberg 2000, Rickels 2000 b, Hackett 1999, Pollack 2001, Rynn 2000). Six trials were excluded: two trials were open studies, without a control group (Hedges 1996; Wingerson 1992); two included patients with GAD plus other types of mental illness (Johnstone 1980 a; Lipman 1986); one study included patients who were stopping long term benzodiazepine therapy (Rickels 2000 a). One study presented early data for an already included study (Hackett 1999). We are waiting for further data for one study (Hoehn-Saric 1988). One study involved children and adolescents with GAD (Rynn 2000) and its results were reviewed separately. Our review showed that antidepressants were better than placebo (dummy treament) for treating GAD and were well tolerated. We did not find evidence to conclude whether some types of antidepressant are better than others. Overall, about 5 people need to be treated in order for one person with GAD to benefit. The single study using antidepressants in children and adolescents with GAD also showed very promising results.

Authors' conclusions: 

The available evidence suggests that antidepressants are superior to placebo in treating GAD. There is evidence from one trial suggesting that paroxetine and imipramine have a similar efficacy and tolerability. There is also evidence from placebo-controlled trials suggesting that these drugs are well tolerated by GAD patients. Further trials of antidepressants for GAD will help to demonstrate which antidepressants should be used for which patients.

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Background: 

Pharmacological treatments have been successfully used to treat Generalized Anxiety Disorder (GAD). Benzodiazepine and non benzodiazepine anxiolytics used to be the mainstay for the pharmacological treatment of GAD. However, data emerging over the last two decades have shown that antidepressants may be as effective as anxiolytics in this condition. The use of antidepressants may also be beneficial , because GAD often coexists with major depressive disorder (62% comorbidity) and dysthymia (37%).

Objectives: 

To assess the efficacy and acceptability of antidepressants for treating generalized anxiety disorder.

Search strategy: 

Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register - CCDANCTR (up to May 2002), Anxiety Neurosis (up to May 2002) and Cochrane Controlled Trials Register (CENTRAL/CCTR) (up to May 2002), MEDLINE (1966 to May 2002), LILACS (1982 to May 2002); reference searching; personal communication; conference abstracts and book chapters on the treatment of generalized anxiety disorder.

Selection criteria: 

Randomized controlled trials were included. Non randomized studies and those that included patients with both GAD and another Axis I co-morbidity were excluded.

Data collection and analysis: 

The data from studies were extracted independently by two reviewers. Relative risks, weighted mean difference and number needed to treat were estimated. People who died or dropped out were regarded as having had no improvement.

Main results: 

Antidepressants (imipramine, venlafaxine and paroxetine) were found to be superior to placebo in treating GAD. The calculated NNT for antidepressants in GAD is 5.15. Dropout rates did not differ between antidepressants. Only one study presented data on imipramine and trazodone. Imipramine was chosen as the reference drug and, therefore, data on trazodone could not be included in the meta analysis. Only one study was conducted among children and adolescents (Rynn 2000). This showed very promising results of sertraline in children and adolescents with GAD, which warrants replication in larger samples.